A phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6 for lower rectal cancer with suspected lateral pelvic node metastasis (JCOG1310, PRECIOUS trial)

INTERVENTION: A: T(S)ME+LND and postoperative chemotherapy (mFOLFOX 12 cycles) B: preoperative chemotherapy (mFOLFOX 6 cycles), T(S)ME+LND, and postoperative chemotherapy (mFOLFOX 6 cycles) CONDITION: Lower rectal cancer with suspected lateral pelvic node metastasis PRIMARY OUTCOME: Phase II: Proportion of patients with R0 resection, Phase III: Overall survival SECONDARY OUTCOME: Phase II part: Proportion of operative complication, Proportion of patients who complete 12 cycles of chemotherapy ; Phase III part: Progression‐free survival, Local progression‐free survival, Proportion of patients with R0 resection, Overall response rate of preoperative chemotherapy (Group B), Pathological complete response rate (Group B), Proportion of patients who complete 12 cycles of chemotherapy, Incidence of adverse events, Incidence of serious adverse events, Proportion of operative complication, Proportion of preservation of adjacent organs, Proportion of anus‐preservation, Proportion of anus‐preservation without stoma INCLUSION CRITERIA: 1. Pathologically proven adenocarcinoma or adenosquamous carcinoma 2. Primary tumor located at Upper rectum, Lower rectum, and Anal canal 3. The lower border of the tumor located between the peritoneal reflection and the anal verge 4. cT2, cT3, and cT4 tumor on contrast‐enhanced CT or MRI, except T4b tumor invading the trigone of bladder, urethra, or sacrum 5. Lateral lymph nodes with 10mm or more in short axis diameter on contrast‐enhanced CT or MRI data of 5mm‐thickness slices (cN3) 6. No distant metastasis on contrast‐enhanced CT or MRI (cM0) 7. Aged 20 to 74 years old 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 9. No prior chemotherapy or treatment such as rectal resection, pelvic lymph node dissection, or pelvic irradiation for any malignancies 10. No other colorectal carcinoma, except cTis or cT1a 11. Adequate organ function as evidenced by the following laboratory studies within 14 days prior to